Factors associated with unintended perianesthesia hypothermia.

Background: Our hypothesis was that total intravenous anesthesia (TIVA) is associated with an increase in hypothermia. Methods: Inclusion criteria were patients from the National Anesthesia Clinical Outcomes Registry undergoing a general anesthetic during 2019. Data collected included patient age, sex, American Society of Anesthesiologists physical status classification system score (ASAPS), duration of anesthetic, use of TIVA, type of procedure, and hypothermia. Continuous variables were compared using Student's t test or Mann Whitney rank sum as appropriate. Mixed effects multiple logistic regression was performed to determine the association between independent variables and hypothermia. Results: There was a low incidence of hypothermia (1.2%). Patients who became hypothermic were older, had a higher median ASAPS, and had a higher rate of TIVA. TIVA patients had a significantly increased odds for hypothermia when controlling for covariates. Patients undergoing obstetrical, thoracic, or radiological procedures had increased odds for hypothermia. In a matched cohort subset, TIVA was associated with a greater rate and increased odds for hypothermia. Conclusions: The novel and noteworthy finding was the association between TIVA and perianesthesia hypothermia. Thoracic, radiologic, and obstetrical procedures were associated with greater rates of and odds for hypothermia. Other identified factors can help to stratify patients for risk for hypothermia.

Functional recovery in a cohort of ECMO and non-ECMO acute respiratory distress syndrome survivors.

BACKGROUND: The mortality benefit of VV-ECMO in ARDS has been extensively studied, but the impact on long-term functional outcomes of survivors is poorly defined. We aimed to assess the association between ECMO and functional outcomes in a contemporaneous cohort of survivors of ARDS. METHODS: Multicenter retrospective cohort study of ARDS survivors who presented to follow-up clinic. The primary outcome was FVC% predicted. Univariate and multivariate regression models were used to evaluate the impact of ECMO on the primary outcome. RESULTS: This study enrolled 110 survivors of ARDS, 34 of whom were managed using ECMO. The ECMO cohort was younger (35 [28, 50] vs. 51 [44, 61] years old, p < 0.01), less likely to have COVID-19 (58% vs. 96%, p < 0.01), more severely ill based on the Sequential Organ Failure Assessment (SOFA) score (7 [5, 9] vs. 4 [3, 6], p < 0.01), dynamic lung compliance (15 mL/cmH20 [11, 20] vs. 27 mL/cmH20 [23, 35], p < 0.01), oxygenation index (26 [22, 33] vs. 9 [6, 11], p < 0.01), and their need for rescue modes of ventilation. ECMO patients had significantly longer lengths of hospitalization (46 [27, 62] vs. 16 [12, 31] days, p < 0.01) ICU stay (29 [19, 43] vs. 10 [5, 17] days, p < 0.01), and duration of mechanical ventilation (24 [14, 42] vs. 10 [7, 17] days, p < 0.01). Functional outcomes were similar in ECMO and non-ECMO patients. ECMO did not predict changes in lung function when adjusting for age, SOFA, COVID-19 status, or length of hospitalization. CONCLUSIONS: There were no significant differences in the FVC% predicted, or other markers of pulmonary, neurocognitive, or psychiatric functional recovery outcomes, when comparing a contemporaneous clinic-based cohort of survivors of ARDS managed with ECMO to those without ECMO.

Sugammadex and blood loss during cervical spine fusion surgery.

Background and Aims: Sugammadex (SUG) has been associated with changes in coagulation studies. Most reports have concluded a lack of clinical significance based on surgical blood loss with SUG use at the end of surgery. Previous reports have not measured its use intraoperatively during ongoing blood loss. Our hypothesis was that the use of SUG intraoperatively may increase bleeding. Material and Methods: This was a single site retrospective study. Inclusion criteria were patients undergoing a primary posterior cervical spine fusion, aged over 18 years, between July 2015 and June 2021. The primary outcomes compared were intraoperative estimated blood loss (EBL) and postoperative drain output (PDO) between patients receiving SUG, neostigmine (NEO) and no NMB reversal agent. The objective was to determine if there was a difference in primary endpoints between patients administered SUG, NEO or no paralytic reversal agent. Primary endpoints were compared using analysis of variance with a P value of 0.05 used to determine statistical significance. Groups were compared using the Chi-squared test, rank sum or student's t test. A logistic regression model was constructed to account for differences between the groups. Results: There was no difference in median EBL or PDO between groups. The use of SUG was not associated with an increase in odds for >500 milliliters (ml) of EBL. Increasing duration of surgery and chronic kidney disease were both associated with an increased risk for EBL >500 ml. Conclusion: Intraoperative use of SUG was not associated with increased bleeding. Any coagulation laboratory abnormalities previously noted did not appear to have an associated clinical significance.

Trajectory of PaO2/FiO2 Ratio in Shock After Angiotensin II.

INTRODUCTION: High-dose catecholamines can impair hypoxic pulmonary vasoconstriction and increase shunt fraction. We aimed to determine if Angiotensin II (Ang-2) is associated with improved PaO2/FiO2 and SpO2/FiO2 in patients in shock. METHODS: Adult patients at four tertiary care centers and one community hospital in the United States who received Ang-2 from July 2018-September 2020 were included in this retrospective, observational cohort study. PaO2, SpO2, and FiO2 were measured at 13 timepoints during the 48-h before and after Ang-2 initiation. Piecewise linear mixed models of PaO2/FiO2 and SpO2/FiO2 were created to evaluate hourly changes in oxygenation after Ang-2 initiation. The difference in the proportion of patients with PaO2/FiO2 ≤ 300 mm Hg at the time of Ang-2 initiation and 48 h after was also examined. RESULTS: The study included 254 patients. In the 48 h prior to Ang-2 initiation, oxygenation was significantly declining (hourly PaO2/FiO2 change -4.7 mm Hg/hr, 95% CI - 6.0 to -3.5, p < .001; hourly SpO2/FiO2 change -3.1/hr, 95% CI-3.7 to -2.4, p < .001). Ang-2 treatment was associated with significant improvements in PaO2/FiO2 and SpO2/FiO2 in the 48-h after initiation (hourly PaO2/FiO2 change +1.5 mm Hg/hr, 95% CI 0.5-2.5, p = .003; hourly SpO2/FiO2 change +0.9/hr, 95% CI 0.5-1.2, p < .001). The difference in the hourly change in oxygenation before and after Ang-2 initiation was also significant (pinteraction < 0.001 for both PaO2/FiO2 and SpO2/FiO2). This improvement was associated with significantly fewer patients having a PaO2/FiO2 ≤ 300 mm Hg at 48 h compared to baseline (mean difference -14.9%, 95% CI -25.3% to -4.6%, p = .011). Subgroup analysis found that patients with either a baseline PaO2/FiO2 ≤ 300 mm Hg or a norepinephrine-equivalent dose requirement >0.2 µg/kg/min had the greatest associations with oxygenation improvement. CONCLUSIONS: Ang-2 is associated with improved PaO2/FiO2 and SpO2/FiO2. The mechanisms for this improvement are not entirely clear but may be due to catecholamine-sparing effect or may also be related to improved ventilation-perfusion matching, intrapulmonary shunt, or oxygen delivery.

Initiating angiotensin II at lower vasopressor doses in vasodilatory shock: an exploratory post-hoc analysis of the ATHOS-3 clinical trial.

BACKGROUND: High dose vasopressors portend poor outcome in vasodilatory shock. We aimed to evaluate the impact of baseline vasopressor dose on outcomes in patients treated with angiotensin II (AT II). METHODS: Exploratory post-hoc analysis of the Angiotensin II for the Treatment of High-Output Shock (ATHOS-3) trial data. The ATHOS-3 trial randomized 321 patients with vasodilatory shock, who remained hypotensive (mean arterial pressure of 55-70 mmHg) despite receiving standard of care vasopressor support at a norepinephrine-equivalent dose (NED) > 0.2 µg/kg/min, to receive AT II or placebo, both in addition to standard of care vasopressors. Patients were grouped into low (≤ 0.25 µg/kg/min; n = 104) or high (> 0.25 µg/kg/min; n = 217) NED at the time of study drug initiation. The primary outcome was the difference in 28-day survival between the AT II and placebo subgroups in those with a baseline NED ≤ 0.25 µg/kg/min at the time of study drug initiation. RESULTS: Of 321 patients, the median baseline NED in the low-NED subgroup was similar in the AT II (n = 56) and placebo (n = 48) groups (median of each arm 0.21 µg/kg/min, p = 0.45). In the high-NED subgroup, the median baseline NEDs were also similar (0.47 µg/kg/min AT II group, n = 107 vs. 0.45 µg/kg/min placebo group, n = 110, p = 0.75). After adjusting for severity of illness, those randomized to AT II in the low-NED subgroup were half as likely to die at 28-days compared to placebo (HR 0.509; 95% CI 0.274-0.945, p = 0.03). No differences in 28-day survival between AT II and placebo groups were found in the high-NED subgroup (HR 0.933; 95% CI 0.644-1.350, p = 0.71). Serious adverse events were less frequent in the low-NED AT II subgroup compared to the placebo low-NED subgroup, though differences were not statistically significant, and were comparable in the high-NED subgroups. CONCLUSIONS: This exploratory post-hoc analysis of phase 3 clinical trial data suggests a potential benefit of AT II introduction at lower doses of other vasopressor agents. These data may inform design of a prospective trial. TRIAL REGISTRATION: The ATHOS-3 trial was registered in the clinicaltrials.gov repository (no. NCT02338843). Registered 14 January 2015.

Raising the bar on fibrinogen: a retrospective assessment of critical hypofibrinogenemia in severely injured trauma patients.

Objectives: Fibrinogen depletion may occur at higher levels than historically referenced. We evaluated hypofibrinogenemia and associated mortality and multiple organ failure (MOF) after severe injury. Methods: Retrospective investigation including 417 adult patients with Injury Severity Score (ISS) >15. Demographics and injury characteristics were collected. Fibrinogen within 30 minutes of admission was described: <150 mg/dL, 150 mg/dL to 200 mg/dL and >200 mg/dL. Primary outcome: 28-day mortality. Secondary outcomes: 28-day MOF and blood product transfusion. Multivariable logistic regression model evaluated association of fibrinogen categories on risk of death, after controlling for confounding variables. Results presented as OR and 95% CIs. Results: Fibrinogen <150 mg/dL: 4.8%, 150 mg/dL to 200 mg/dL: 18.2%, >200 mg/dL: 77.0%. 28-day mortality: 15.6%. Patients with <150 mg/dL fibrinogen had over fourfold increased 28-day mortality risk (OR: 4.9, 95% CI 1.53 to 15.7) after adjusting for age, ISS and admission Glasgow Coma Scale. Patients with lower fibrinogen were more likely to develop MOF (p=0.04) and receive larger red blood cell transfusion volumes at 3 hours and 24 hours (p<0.01). Conclusions: Fibrinogen <150 mg/dL is significantly associated with increased 28-day mortality. Patients with fibrinogen <150 mg/dL were more likely to develop MOF and required increased administration of blood products. The optimal threshold for critically low fibrinogen, the association with MOF and subsequent fibrinogen replacement requires further investigation. Level of evidence: Level III.

Thromboelastography Parameters do not Discriminate for Thrombotic Events in Hospitalized Patients With COVID-19.

BACKGROUND: Coronavirus disease 2019 (COVID-19) is associated with a prothrombotic state; leading to multiple sequelae. We sought to detect whether thromboelastography (TEG) parameters would be able to detect thromboembolic events in patients hospitalized with COVID-19. METHODS: We performed a retrospective multicenter case-control study of the Collaborative Research to Understand the Sequelae of Harm in COVID (CRUSH COVID) registry of 8 tertiary care level hospitals in the United States (US). This registry contains adult patients with COVID-19 hospitalized between March 2020 and September 2020. RESULTS: A total of 277 hospitalized COVID-19 patients were analyzed to determine whether conventional coagulation TEG parameters were associated with venous thromboembolic (VTE) and thrombotic events during hospitalization. A clotting index (CI) >3 was present in 45.8% of the population, consistent with a hypercoagulable state. Eighty-three percent of the patients had clot lysis at 30 min (LY30) = 0, consistent with fibrinolysis shutdown, with a median of 0.1%. We did not find TEG parameters (LY30 area under the receiver operating characteristic [ROC] curve [AUC] = 0.55, 95% CI: 0.44-0.65, P value = .32; alpha angle [α] AUC = 0.58, 95% CI: 0.47-0.69, P value = .17; K time AUC = 0.58, 95% CI: 0.46-0.69, P value = .67; maximum amplitude (MA) AUC = 0.54, 95% CI: 0.44-0.64, P value = .47; reaction time [R time] AUC = 0.53, 95% CI: 0.42-0.65, P value = .70) to be a good discriminator for VTE. We also did not find TEG parameters (LY30 AUC = 0.51, 95% CI: 0.42-0.60, P value = .84; R time AUC = 0.57, 95%CI: 0.48-0.67, P value .07; α AUC = 0.59, 95%CI: 0.51-0.68, P value = .02; K time AUC = 0.62, 95% CI: 0.53-0.70, P value = .07; MA AUC = 0.65, 95% CI: 0.57-0.74, P value < .01) to be a good discriminator for thrombotic events. CONCLUSIONS: In this retrospective multicenter cohort study, TEG in COVID-19 hospitalized patients may indicate a hypercoagulable state, however, its use in detecting VTE or thrombotic events is limited in this population.

Angiotensin II for Vasodilatory Hypotension in Patients Requiring Mechanical Circulatory Support.

Background: Patients supported on mechanical circulatory support devices experience vasodilatory hypotension due to high surface area exposure to nonbiological and non-endothelialized surfaces. Angiotensin II has been studied in general settings of vasodilatory shock, however concerns exist regarding the use of this vasopressor in patients with pre-existing cardiac failure. The objective of this study was to assess the systemic and central hemodynamic effects of angiotensin II in patients with primary cardiac or respiratory failure requiring treatment with mechanical circulatory support devices. Methods: Multicenter retrospective observational study of adults supported on a mechanical circulatory support device who received angiotensin II for vasodilatory shock. The primary outcome was the intraindividual change from baseline in mean arterial pressure (MAP) and vasopressor dosage after angiotensin II. Results: Fifty patients were included with mechanical circulatory devices that were primarily used for cardiac failure (n = 41) or respiratory failure (n = 9). At angiotensin II initiation, the norepinephrine equivalent vasopressor dosage was 0.44 (0.34, 0.64) and 0.47 (0.33, 0.73) mcg/kg/min in the cardiac and respiratory groups, respectively. In the cardiac group, MAP increased from 60 to 70 mmHg (intraindividual P < .001) in the 1 h after angiotensin II initiation and the vasopressor dosage declined by 0.04 mcg/kg/min (intraindividual P < .001). By 12 h, the vasopressor dosage declined by 0.16 mcg/kg/min (P = .001). There were no significant changes in cardiac index or mean pulmonary artery pressure throughout the 12 h following angiotensin II. In the respiratory group, similar but nonsignificant effects at 1 h on MAP (61-81 mmHg, P = .26) and vasopressor dosage (decline by 0.13 mcg/kg/min, P = .06) were observed. Conclusions: In patients requiring mechanical circulatory support for cardiac failure, angiotensin II produced beneficial systemic hemodynamic effects without negatively impacting cardiac function or pulmonary pressures. The systemic hemodynamic effects in those with respiratory failure were nonsignificant due to limited sample size.

Preoperative Pressure Ulcers, Mortality, and Complications in Older Hip Fracture Surgery Patients.

INTRODUCTION: The effect of a preoperative pressure ulcer (PPU) in hip fracture patients on postoperative outcomes has not been well studied. We hypothesized that the presence of a PPU would be associated with increased mortality and serious complications in hip fracture surgery patients. METHODS: We conducted a cohort study of 19,520 hip fracture patients from 2016 to 2019 with data from the National Surgical Quality Improvement Program. The study exposure was the presence of a PPU. This study's primary outcome was 30-day mortality. Secondary outcomes included deep vein thrombosis (DVT), pulmonary embolism, surgical site infection, pneumonia, and unplanned hospital readmission. Propensity score analysis and inverse probability of treatment weighting were used to control for confounding and reduce bias. RESULTS: The presence of a PPU was independently associated with a 21% increase in odds of 30-day mortality (odds ratio (OR) = 1.2, P = 0.004). The presence of a PPU was also independently associated with increased odds of DVT (OR = 1.59, P < 0.001), pneumonia (OR = 1.39, P < 0.001), and unplanned hospital readmission (OR = 1.43, P < 0.001) and a significant increase in the mean length of hospital stay of 0.4 days (P = 0.007). DISCUSSION: We found that PPUs were independently associated with increased 30-day mortality, DVT, pneumonia, hospital length of stay, and unplanned hospital readmission.

Socioeconomic Disparities in Method of Anesthesia for Knee Arthroplasties in the US.

INTRODUCTION: Knee arthroplasty (KA) can be performed using general anesthesia (GA), neuraxial anesthesia (NA) or regional anesthesia (RA). We believe proportion of types of anesthetics have changed but that there is a disparity based on socioeconomic factors. METHODS: Unadjusted rates and adjusted odds ratios for the use of RA or PNB were compared between groupings of patients based on socioeconomic status. RESULTS: General anesthesia is the most common (49.7%) while NA (39.4%) and RA (10.9%) were the second and third. University hospitals and patient home ZIP Code median income had the strongest association with RA as a (adjusted odds ratio (AOR) 26.3, 95% confidence interval (95%CI) 22.1-31.3, p<.01 and AOR 7.58, 95% CI 7.20-7.98, p<.01). CONCLUSION: General anesthesia is the most common but the rate of alternative forms of primary anesthesia type have changed over time. Disparities exist in anesthesia care which are associated with income levels.

Association of Early Aspirin Use With In-Hospital Mortality in Patients With Moderate COVID-19.

Importance: Prior observational studies suggest that aspirin use may be associated with reduced mortality in high-risk hospitalized patients with COVID-19, but aspirin's efficacy in patients with moderate COVID-19 is not well studied. Objective: To assess whether early aspirin use is associated with lower odds of in-hospital mortality in patients with moderate COVID-19. Design, Setting, and Participants: Observational cohort study of 112 269 hospitalized patients with moderate COVID-19, enrolled from January 1, 2020, through September 10, 2021, at 64 health systems in the United States participating in the National Institute of Health's National COVID Cohort Collaborative (N3C). Exposure: Aspirin use within the first day of hospitalization. Main Outcome and Measures: The primary outcome was 28-day in-hospital mortality, and secondary outcomes were pulmonary embolism and deep vein thrombosis. Odds of in-hospital mortality were calculated using marginal structural Cox and logistic regression models. Inverse probability of treatment weighting was used to reduce bias from confounding and balance characteristics between groups. Results: Among the 2 446 650 COVID-19-positive patients who were screened, 189 287 were hospitalized and 112 269 met study inclusion. For the full cohort, Median age was 63 years (IQR, 47-74 years); 16.1% of patients were African American, 3.8% were Asian, 52.7% were White, 5.0% were of other races and ethnicities, 22.4% were of unknown race and ethnicity. In-hospital mortality occurred in 10.9% of patients. After inverse probability treatment weighting, 28-day in-hospital mortality was significantly lower in those who received aspirin (10.2% vs 11.8%; odds ratio [OR], 0.85; 95% CI, 0.79-0.92; P < .001). The rate of pulmonary embolism, but not deep vein thrombosis, was also significantly lower in patients who received aspirin (1.0% vs 1.4%; OR, 0.71; 95% CI, 0.56-0.90; P = .004). Patients who received early aspirin did not have higher rates of gastrointestinal hemorrhage (0.8% aspirin vs 0.7% no aspirin; OR, 1.04; 95% CI, 0.82-1.33; P = .72), cerebral hemorrhage (0.6% aspirin vs 0.4% no aspirin; OR, 1.32; 95% CI, 0.92-1.88; P = .13), or blood transfusion (2.7% aspirin vs 2.3% no aspirin; OR, 1.14; 95% CI, 0.99-1.32; P = .06). The composite of hemorrhagic complications did not occur more often in those receiving aspirin (3.7% aspirin vs 3.2% no aspirin; OR, 1.13; 95% CI, 1.00-1.28; P = .054). Subgroups who appeared to benefit the most included patients older than 60 years (61-80 years: OR, 0.79; 95% CI, 0.72-0.87; P < .001; >80 years: OR, 0.79; 95% CI, 0.69-0.91; P < .001) and patients with comorbidities (1 comorbidity: 6.4% vs 9.2%; OR, 0.68; 95% CI, 0.55-0.83; P < .001; 2 comorbidities: 10.5% vs 12.8%; OR, 0.80; 95% CI, 0.69-0.93; P = .003; 3 comorbidities: 13.8% vs 17.0%, OR, 0.78; 95% CI, 0.68-0.89; P < .001; >3 comorbidities: 17.0% vs 21.6%; OR, 0.74; 95% CI, 0.66-0.84; P < .001). Conclusions and Relevance: In this cohort study of US adults hospitalized with moderate COVID-19, early aspirin use was associated with lower odds of 28-day in-hospital mortality. A randomized clinical trial that includes diverse patients with moderate COVID-19 is warranted to adequately evaluate aspirin's efficacy in patients with high-risk conditions.

Racial disparities in catheter related urinary tract infections among elderly trauma patients in the US.

BACKGROUND: Catheter associated urinary tract infections (CAUTIs) have become a focus for reducing healthcare costs. Reimbursement may be reduced to hospitals with higher rates. The implementation of bundles or other efforts to reduce infection numbers may not be as robust at hospitals caring for more diverse patient populations. This may lead to a disparity in hospital-associated infections rates that may lead to lower reimbursement and a downward spiral of quality of care and racial disparities. METHODS: We analyzed patients in the National Trauma Data Bank from 2016 to 2017. The final analysis included patients 65 years or older with one or more day of mechanical ventilation. This was the population had the highest rate of CAUTI. We compared white patients to non-whites using students t test, Mann Whitney U test, or chi-square as appropriate. Logistic regression with odds ratios (ORs) and 95% confidence intervals (CI) was computed to identify risk factors for of CAUTI. RESULTS: Risk factors for developing a CAUTI were race (OR 1.44, 95% confidence interval (95%CI) 1.23-1.71), injury severity score (OR 1.10 per increase of one, 95% CI 1.01-1.02), care at a teaching hospital (OR 1.17, 95%CI 1.02-1.35), private insurance (OR 1.28, 95%CI 1.09-1.51), hypertension (OR 1.18, 95%CI 1.02-1.37), female gender (OR 1.54, 95%CI 1.33-1.77). Non-white patients received care at teaching hospitals more often and had a higher rate of government insurance or no insurance. DISCUSSION: The Center for Medicare and Medicaid Services (CMS) has put in place a reimbursement modification 87 plan based on the rates of hospital-associated infections including CAUTIs. We have demonstrated non-white 88 patients have higher odds for developing a CAUTI. CONCLUSION: CMS may potentially worsen the racial disparity by further cutting reimbursement to hospitals who care for higher proportions of non-whites.

Effects of a single bolus of hydroxocobalamin on hemodynamics in vasodilatory shock.

PURPOSE: Hydroxocobalamin has been observed to cause transient hypertension in healthy subjects, but rigorous studies examining its efficacy are lacking. MATERIALS AND METHODS: Adults in shock who received hydroxocobalamin from 2017 to 2021 were analyzed retrospectively. Hourly hemodynamics from 24 h before and after treatment were collected, and the difference and hourly change of mean arterial pressure (MAP), systolic blood pressure (SBP), diastolic blood pressure (DBP), and norepinephrine-equivalent dose (NED) were examined in mixed-effects models. RESULTS: This study included 3992 hemodynamic data points from 35 patients and is the largest case series to date. In the mixed effects model, there was no difference in MAP 24-h after hydroxocobalamin administration (estimated fixed effect [EFE] -0.2 mmHg, p = 0.89). A two-piecewise mixed model found that the hourly change in MAP was not different from zero in either the pre-administration (EFE 0.0 mmHg/h, p = 0.80) or post-administration segments (EFE 0.0 mmHg/h, p = 0.55). Analysis of the SBP, DBP, and NED also found similar insignificant results. CONCLUSIONS: Although hydroxocobalamin has been observed to cause hypertension in healthy subjects, our results suggest that in patients with shock, hydroxocobalamin may not be effective in improving hemodynamics at 24 h after administration.

A Multicenter Observational Cohort Study of Angiotensin II in Shock.

INTRODUCTION: Angiotensin II (Ang-2) is a non-catecholamine vasopressor that targets the renin-angiotensin-aldosterone system by agonism of the angiotensin type 1 receptor. Its utility as a vasopressor and a catecholamine-sparing agent was demonstrated in the pivotal ATHOS-3 trial, and numerous post-hoc analyses have shown reduced mortality in certain subsets of the population. METHODS: Consecutive adult patients at 5 centers who received Ang-2 from 2017-2020 were included in this multicenter, retrospective observational cohort study. Patient demographics, hemodynamics, and adverse events were collected. The primary outcomes of the study were the mean difference in MAP and norepinephrine (NEpi)-equivalent dose at hours 0 and 3 following initiation of Ang-2 therapy. RESULTS: One hundred and sixty-two patients were included in this study. The primary outcomes of an increase in MAP (mean difference 9.3 mmHg, 95% CI 6.4-12.1, p < 0.001) and a reduction in NEpi equivalent dose (mean difference 0.16 µg/kg/min, 95% CI 0.10-0.22, p < 0.001) between hours 0 and 3 were statistically significant. The median time to reach a MAP ≥65 was 16 minutes (IQR 5-60 min). After stratifying patients by the NED dose and number of vasopressors administered prior to the initiation of Ang-2, those with a NED dose < 0.2 µg/kg/min, NED dose < 0.3 µg/kg/min, or those on ≤ 3 vasopressors had a significantly greater reduction in NED by hour 3 than those patients above these thresholds. CONCLUSION: Ang-2 is an effective vasopressor and reduces catecholamine dose significantly. Its effect is rapid, with target MAP obtained within 30 minutes in most patients. Given the critical importance of adequate blood pressure to organ perfusion, Ang-2 should be considered when target MAP cannot be achieved with conventional vasopressors. Ang-2 should be utilized early in the course of shock, before the NED dose exceeds 0.2-0.3 µg/kg/min and before the initiation of the fourth-line vasopressor.

Renin Kinetics Are Superior to Lactate Kinetics for Predicting In-Hospital Mortality in Hypotensive Critically Ill Patients.

OBJECTIVES: Whole blood lactate concentration is widely used in shock states to assess perfusion. We aimed to determine if the change in plasma renin concentration over time would be superior to the change in lactate concentration for predicting in-hospital mortality in hypotensive patients on vasopressors. DESIGN: Prospective, observational cohort study. SETTING: Tertiary academic ICU. PATIENTS: Adult patients on vasopressors for greater than 6 hours to maintain a mean arterial pressure greater than or equal to 65 mm Hg during January 2020. INTERVENTIONS: Plasma renin concentrations were measured at enrollment and at 24, 48, and 72 hours. Whole blood lactate measurements were performed according to normal standard of care. Logistic regression was performed to evaluate whether the change in renin or lactate concentration could predict in-hospital mortality. Generalized estimating equations were used to analyze the association between renin and lactate concentration and in-hospital mortality. The area under the receiver operating characteristics curve was performed to measure the discriminative ability of initial and peak renin and lactate concentration to predict mortality. The association between renin and lactate concentration above the upper limit of normal at each timepoint with in-hospital mortality was also examined. MEASUREMENTS AND MAIN RESULTS: The study included 197 renin and 148 lactate samples obtained from 53 patients. The slope of the natural log (ln) of renin concentration was independently associated with mortality (adjusted odds ratio, 10.35; 95% CI, 1.40-76.34; p = 0.022), but the slope of ln-lactate concentration was not (adjusted odds ratio, 4.78; 95% CI, 0.03-772.64; p = 0.55). The generalized estimating equation models found that both ln-renin (adjusted odds ratio, 1.18; 95% CI, 1.02-1.37; p = 0.025) and ln-lactate (adjusted odds ratio, 2.38; 95% CI, 1.05-5.37; p = 0.037) were associated with mortality. Area under the receiver operating characteristics curve analysis demonstrated that initial renin could predict in-hospital mortality with fair discrimination (area under the receiver operating characteristics curve, 0.682; 95% CI, 0.503-0.836; p = 0.05), but initial lactate could not (area under the receiver operating characteristics curve, 0.615; 95% CI, 0.413-0.803; p = 0.27). Peak renin (area under the receiver operating characteristics curve, 0.728; 95% CI, 0.547-0.888; p = 0.01) and peak lactate (area under the receiver operating characteristics curve, 0.746; 95% CI, 0.584-0.876; p = 0.01) demonstrated moderate discrimination. There was no significant difference in discriminative ability between initial or peak renin and lactate concentration. At each study time point, a higher proportion of renin values exceeded the threshold of normal (40 pg/mL) in nonsurvivors than in survivors, but this association was not significant for lactate. CONCLUSIONS: Although there was no significant difference in the performance of renin and lactate when examining the absolute values of each laboratory, a positive rate of change in renin concentration, but not lactate concentration, over 72 hours was associated with in-hospital mortality. For each one-unit increase in the slope of ln-renin, the odds of mortality increased 10-fold. Renin levels greater than 40 pg/mL, but not lactate levels greater than 2 mmol/L, were associated with in-hospital mortality. These findings suggest that plasma renin kinetics may be superior to lactate kinetics in predicting mortality of hypotensive, critically ill patients.

The Algorithm Examining the Risk of Massive Transfusion (ALERT) Score Accurately Predicts Massive Transfusion at the Scene of Injury and on Arrival to the Trauma Bay: A Retrospective Analysis.

BACKGROUND: Massive transfusion (MT) is required to resuscitate traumatically injured patients with complex derangements. Scoring systems for MT typically require laboratory values and radiological imaging that may delay the prediction of MT. STUDY DESIGN: The Trauma ALgorithm Examining the Risk of massive Transfusion (Trauma ALERT) study was an observational cohort study. Prehospital and admission ALERT scores were constructed with logistic regression of prehospital and admission vitals, and FAST examination results. Internal validation was performed with bootstrap analysis and cross-validation. RESULTS: The development cohort included 2,592 patients. Seven variables were included in the prehospital ALERT score: systolic blood pressure (SBP), diastolic blood pressure (DBP), heart rate (HR), respiratory rate (RR), SpO2, motor Glasgow Coma Scale (GCS) score, and penetrating mechanism. Eight variables from 2,307 patients were included in the admission ALERT score: admission SBP, HR, RR, GCS score, temperature, FAST examination result, and prehospital SBP and DBP.The area under the receiving operator characteristic curve for the prehospital and admission models were 0.754 (95% bootstrapped CI 0.735-0.794, P < 0.001) and 0.905 (95% bootstrapped CI 0.867-0.923, P < 0.001), respectively. The prehospital ALERT score had equivalent diagnostic accuracy to the ABC score (P = 0.97), and the admission ALERT score outperformed both the ABC and the prehospital ALERT scores (P < 0.0001). CONCLUSION: The prehospital and admission ALERT scores can accurately predict massive transfusion in trauma patients without the use of time-consuming laboratory studies, although prospective studies need to be performed to validate these findings. Early identification of patients who will require MT may allow for timely mobilization of scarce resources and could benefit patients by making blood products available for treating hemorrhagic shock.

Association of prehospital antiplatelet therapy with survival in patients hospitalized with COVID-19: A propensity score-matched analysis.

PURPOSE: Coronavirus disease 2019 (COVID-19) is associated with hypercoagulability and increased thrombotic risk. The impact of prehospital antiplatelet therapy on in-hospital mortality is uncertain. METHODS: This was an observational cohort study of 34 675 patients ≥50 years old from 90 health systems in the United States. Patients were hospitalized with laboratory-confirmed COVID-19 between February 2020 and September 2020. For all patients, the propensity to receive prehospital antiplatelet therapy was calculated using demographics and comorbidities. Patients were matched based on propensity scores, and in-hospital mortality was compared between the antiplatelet and non-antiplatelet groups. RESULTS: The propensity score-matched cohort of 17 347 patients comprised of 6781 and 10 566 patients in the antiplatelet and non-antiplatelet therapy groups, respectively. In-hospital mortality was significantly lower in patients receiving prehospital antiplatelet therapy (18.9% vs. 21.5%, p < .001), resulting in a 2.6% absolute reduction in mortality (HR: 0.81, 95% CI: 0.76-0.87, p < .005). On average, 39 patients needed to be treated to prevent one in-hospital death. In the antiplatelet therapy group, there was a significantly lower rate of pulmonary embolism (2.2% vs. 3.0%, p = .002) and higher rate of epistaxis (0.9% vs. 0.4%, p < .001). There was no difference in the rate of other hemorrhagic or thrombotic complications. CONCLUSIONS: In the largest observational study to date of prehospital antiplatelet therapy in patients with COVID-19, there was an association with significantly lower in-hospital mortality. Randomized controlled trials in diverse patient populations with high rates of baseline comorbidities are needed to determine the ultimate utility of antiplatelet therapy in COVID-19.

Seven-Year Follow-Up of an Online Critical Care Curriculum.

Background: In July of 2013, the University of Maryland launched MarylandCCProject.com. This free-access educational website delivers asynchronous high-quality multidisciplinary critical care education targeted at critical care trainees. The lectures, presented in real time on-site, are recorded and available on the website or as a podcast on iTunes or Android. Thus, the curriculum can be easily accessed around the world.Objective: We sought to identify the impact this website has on current and former University of Maryland critical care trainees.Methods: A 32-question survey was generated using a standard survey generation tool. The survey was e-mailed in the fall of 2019 to the University of Maryland Multi-Departmental Critical Care current and graduated trainees from the prior 7 years. Survey data were collected through December 2019. The questions focused on user demographics, overall experience with the website, scope of website use, and clinical application of the content. Anonymous responses were electronically gathered.Results: A total of 186 current trainees and graduates were surveyed, with a 39% (n = 72) response rate. Of responders, 76% (55) use the website for ongoing medical education. The majority use the website at least monthly. Most users (63%, n = 35) access the lectures directly through the website. All 55 current users agree that the website has improved their medical knowledge and is a useful education resource. Platform use has increased and includes users from around the world.Conclusion: Based on our current data, the MarylandCCProject remains a valuable and highly used educational resource, impacting patient care both during and after critical care fellowship training.

The Impact of Corticosteroids on Secondary Infection and Mortality in Critically Ill COVID-19 Patients.

BACKGROUND: Corticosteroids are part of the treatment guidelines for COVID-19 and have been shown to improve mortality. However, the impact corticosteroids have on the development of secondary infection in COVID-19 is unknown. We sought to define the rate of secondary infection in critically ill patients with COVID-19 and determine the effect of corticosteroid use on mortality in critically ill patients with COVID-19. STUDY DESIGN AND METHODS: One hundred and thirty-five critically ill patients with COVID-19 admitted to the Intensive Care Unit (ICU) at the University of Maryland Medical Center were included in this single-center retrospective analysis. Demographics, symptoms, culture data, use of COVID-19 directed therapies, and outcomes were abstracted from the medical record. The primary outcomes were secondary infection and mortality. Proportional hazards models were used to determine the time to secondary infection and the time to death. RESULTS: The proportion of patients with secondary infection was 63%. The likelihood of developing secondary infection was not significantly impacted by the administration of corticosteroids (HR 1.45, CI 0.75-2.82, P = 0.28). This remained consistent in sub-analysis looking at bloodstream, respiratory, and urine infections. Secondary infection had no significant impact on the likelihood of 28-day mortality (HR 0.66, CI 0.33-1.35, P = 0.256). Corticosteroid administration significantly reduced the likelihood of 28-day mortality (HR 0.27, CI 0.10-0.72, P = 0.01). CONCLUSION: Corticosteroids are an important and lifesaving pharmacotherapeutic option in critically ill patients with COVID-19, which have no impact on the likelihood of developing secondary infections.